Is biocide resistance already a clinical problem?

Transcription

1 Is biocide resistance already a clinical problem? Stephan Harbarth, MD MS University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland

2 Important points Biocide resistance exists Antibiotic resistance is common and clinically more important than biocide resistance Resistance to disinfectants is not yet a major clinical problem in healthcare Cross- and co-resistance between biocides and antibiotics exist and should be carefully monitored

3 Courtesy: M. Wilcox

4 Tschudin-Sutter S, Infect Control Hosp Epidemiol 2011; 32:

5 Fact n 1: MDRO trends MRSA ESBL-producers Carbapenem-resistant Gram-negatives Multiresistant Acinetobacter spp Clostridium difficile Not an increasing problem because of cross-resistance to disinfectants

6 Klebsiella pneumoniae 3 rd Generation Cephalosporin Resistance in Europe Euro Antimicrob Resist Surv Syst (EARSS) & anresis.ch

7 KPC in the U.S., Braykov NP et al. Infect Control Hosp Epidemiol 2013; 34(3):

8 Courtesy:JH Song

9 KPC & NDM control Routine disinfectants are effective against highly resistant carbapenamase-producing Klebsiella pneumoniae (KPC) isolates Routine disinfection methods are effective to control outbreaks of highly resistant organisms such as NDM-1 Klebsiella spp VSW Koo, BJU International 2012; 110: E922-E926 A Robustillo Rodela et al. Euro Surveillance 2012; 17 (7): pii=20086

10 Agenda Antibiotic resistance is common and clinically more important Resistance to disinfectants is not yet a major problem in healthcare

11 Does microbial resistance to biocides creates a hazard in infection control? The current risks to healthcare delivery caused by resistance related to biocides are low, provided that biocides are used under appropriate conditions. Meyer B & Cookson B. J Hosp Infect. 2010; 76: 200-5

12 Fact n 2 Alcohol based hand rubs do not exacerbate the spread of treatmentresistant pathogens, as the overuse of antibiotics does. Alcohol kills germs in a different way, by disrupting cell membranes, a process to which organisms are almost as unlikely to become immune as humans are to become immune against bullets. D Owen. Annals of Health. The New Yorker, 4 March 2013.

13 Sroka S et al, J Hosp Infect 2010; 74:

14 Chlorhexidine resistance Are low-level mupirocin and chlorhexidine resistance associated with MRSA decolonisation failure? Lee & Harbarth. Clinical Infectious Diseases 2011;52(12):

15 Independent risk factors associated with persistent MRSA colonization Multivariate analysis Risk factor OR (95% CI) p value Mupirocin/chlorhex. resistance 3.4 ( ) Age (per 1 year increment) 1.04 ( ) Prior hospitalisation (2 years) 2.4 ( ) 0.04 Wound/pressure sore 5.7 ( ) MRSA-inactive antibiotics 3.1 ( ) 0.01 Central venous catheter 5.7 ( ) 0.02 Lee & Harbarth. Clin Infect Dis 2011;52(12):

16 Efficacy and Limitation of a Chlorhexidine-Based Decolonization Strategy in Preventing Transmission of MRSA in an ICU Retrospective interrupted time-series study Reduced acquisition of endemic MRSA strain (IRR 0.3; 95% CI ) 4-fold increased acquisition of epidemic MRSA strain chlorhexidine MBCs increased 3-fold Plasmid-borne gene: qaca/b Batra R, Cooper BS, Whiteley C, et al. Clin Infect Dis 2010; 50:

17 2004: CHX as skin cleanser of choice for CVLs and PACs. 2005: CHX mouthwash instituted for all AML patients daily. 2011: Daily CHX bathes for neutropenic AML patients. Pediatr Infect Dis J 2013; 32:

18 Fact n 3 No data show that antibiotic-resistant bacteria are less sensitive to disinfectants than antibiotic-sensitive bacteria at currently used germicide contact conditions and concentrations

19 Bactericidal activities of disinfectants against VRE Assessment of the bactericidal activities of 35 commercially available disinfectants No differences in bactericidal time for activity against vancomycin-resistant versus vancomycin-susceptible enterococci VRE strains demonstrating slightly reduced susceptibility to germicides readily inactivated at concentrations of germicides used in hospitals Y. Sakagami et al. J Hosp Infect 2002; 50:

20 E.faecium BSI isolates, Austin Hospital by time and alcohol log kill incomplete hand hygiene may lead to alcohol escape 5 minute isopropyl alcohol kill assay (final concentration 23%) Courtesy: P Johnson

21 Bacterial Contamination of Keyboards: Efficacy and Functional Impact of Disinfectants Disinfectants containing alcohol, chlorine, phenol or quaternary ammonium effective at removing MRSA, P. aeruginosa and VRE on contaminated PC keyboards Excellent sustained activity of quaternary ammonium containing products against VRE and P. aeruginosa for up to 48 h Rutala A et al; Infect Control Hosp Epidemiol 2006; 27:

22 Correlation between reduced susceptibility to disinfectants and multidrug resistance of Acinetobacter Testing susceptibility of 283 clinical isolates of Acinetobacter spp against 4 disinfectants: Only 10% (28) of the isolates had reduced susceptibility to the disinfectants MIC 90 of the disinfectants was lower than their in-use concentration Kawamura-Sato K et al. J Antimicrob Chemother 2012; 65:

23 Fact n 4 Cross- and co-resistance between antiseptics and antibiotics exists and should be carefully monitored

24 Relationship between biocide resistance and antibiotic resistance In laboratory experiments, antibiotic resistance following biocide exposure has been described: Cross-resistance: selection of genes encoding resistance to both the biocidal substance and one or more antibiotics Co-resistance: selection for clones or mobile elements also carrying antimicrobial resistance. Indirect selection for bacterial sub-population following biocide exposure resulting in a decrease in susceptibility to both biocides and antibiotics.

25 Co-resistance Co-resistance: mechanisms encoding resistance are genetically linked Tolerance to quarternary ammonium compounds in Gram-negative bacteria qac-genes linked to sulphonamide resistance on mobile genetic elements Sidhu et al. 2001, Sidhu et al. 2002

26 Courtesy: M. Wilcox

27 Link between biocide and antibiotic resistance: open questions Impossible to determine which biocides create the highest risk of generating antibiotic resistance Horizontal gene transfer means that biocides could become triggers of bacterial resistance (e.g. triclosan) More data urgently needed

28 Summary Biocide resistance exists, but antibiotic resistance is clinically more important Increase in antibiotic resistance in clinically important bacteria is not associated with increasing resistance to biocides Resistance to disinfectants is not (yet) a major problem in healthcare CAVE: Chlorhexidine resistance Cross- and co-resistance between disinfectants and antibiotics exist and should be monitored

29 Further Reading

30 Further Reading (2)